Wednesday, May 13, 2020

WHERE THE COVID-19 SPIKE ENTERS THE HOST CELL.

. 2020 May;80(5):554-562.
 doi: 10.1016/j.jinf.2020.02.026. Epub 2020 Mar 10.

COVID-19 Spike-Host Cell Receptor GRP78 Binding Site Prediction

Ibrahim M Ibrahim 1, Doaa H Abdelmalek 1, Mohammed E Elshahat 1, Abdo A Elfiky 2
Affiliations 

Abstract

Objectives: Understanding the novel coronavirus (COVID-19) mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition.
Methods: In this study, the COVID-19 spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The COVID-19 spike protein is modeled using its counterpart, the SARS spike.
Results: Sequence and structural alignments show that four regions, in addition to its cyclic nature have sequence and physicochemical similarities to the cyclic Pep42. Protein-protein docking was performed to test the four regions of the spike that fit tightly in the GRP78 Substrate Binding Domain β (SBDβ). The docking pose revealed the involvement of the SBDβ of GRP78 and the receptor-binding domain of the coronavirus spike protein in recognition of the host cell receptor.
Conclusions: We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These nine residues can be used to develop therapeutics specific against COVID-19.
Keywords: BiP; COVID-19 spike; GRP78; Pep42; Protein-protein docking; Structural bioinformatics.

Conflict of interest statement

Declaration of Competing Interests All of the authors declare that there is no competing interest in this work.

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How the SARScoV-2 breaks into human cells.


Scientists figure out how new coronavirus breaks into human cells

By  
It could aid in drug development.
3D render of the structure of a coronavirus.
(Image: © Shutterstock)
Scientists have revealed the first picture of how the new coronavirus SARS-CoV-2 binds with human respiratory cells in order to hijack them to produce more viruses. 
Researchers led by Qiang Zhou, a research fellow at Westlake University in Hangzhou, China, have revealed how the new virus attaches to a receptor on respiratory cells called angiotensin-converting enzyme 2, or ACE2. 




"They have pictures all the way down at the level of the atoms that interact at the binding interface," Thomas Gallagher, a virologist at Loyola University Chicago who was not involved in the new research but studies coronavirus structure, told Live Science. That level of information is unusual at this stage of a new virus outbreak, he said. 
"The virus outbreak only began to occur a couple months ago, and within that short period of time, these authors have come up with information that I think traditionally takes much longer," Gallagher said. 
That's important, he said, because understanding how the virus enters cells can contribute to research on drugs or even a vaccine for the virus. 
ALL ABOUT CORONAVIRUS

A viral entryway

To infect a human host, viruses must be able to gain entry into individual human cells. They use these cells' machinery to produce copies of themselves, which then spill out and spread to new cells. 
On Feb. 19 in the journal Science, a research team led by scientists at the University of Texas at Austin described the tiny molecular key on SARS-CoV-2 that gives the virus entry into the cell. This key is called a spike protein, or S-protein. Last week, Zhou and his team described the rest of the puzzle: the structure of the ACE2 receptor protein (which is on the surfaces of respiratory cells) and how it and the spike protein interact. The researchers published their findings in the journal Science on March 4. 
"If we think of the human body as a house and 2019-nCoV [another name for SARS-CoV-2] as a robber, then ACE2 would be the doorknob of the house's door. Once the S-protein grabs it, the virus can enter the house," Liang Tao, a researcher at Westlake University who was not involved in the new study, said in a statement.
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